While recent advances in science and technology are helping to improve quality and add years to human lives, the prevention of atherosclerosis, the underlying cause of cardiovascular disease ("CVD"), has not been properly addressed and remains the leading cause of disability and death among middle-aged men. Cardiovascular disease is the leading contributor towards spiralling health care costs, estimated at approximately $17 billion in Canada and remains the most common single cause of death in both men and women. Each year, more than 1,000,000 coronary angiography procedures, approximately 400,000 angioplasties and 400,000 coronary artery bypass operations are performed in the United States alone. The 1992 statistics in Washington State indicate that CVD mortality accounts for 40% of all mortality with overall CVD death slightly more common in women than in men. By the age of 60, one in five men in the United States had experienced a coronary event compared to only one in 17 women. After the age of 60, death from coronary heart disease is one in four for both men and women.
Research to date suggests that cholesterol may play a primary role in atherosclerosis by forming a atherosclerotic plaques in blood vessels, ultimately cutting off blood supply to the heat muscle or alternatively to the brain or legs, depending on the location of the plaque in the arterial tree.sup.1,2. Recent overviews have indicated that a 1% reduction in a person's total serum cholesterol level yields a 2-3% reduction in risk of coronary artery disease.sup.3. Statistically, a 10% decrease in average serum cholesterol (e.g. from 6.0 mmol/L to 5.4 mmol/L) may result in the prevention of 100,000 deaths in the United States annually.sup.4. FNT 1. Law M. R., Wald N. J., Wu T., Hackshaw A., Bailey A.; Systemic underestimation of association between serum cholesterol concentration and ischemic heart disease in observational studies: Dam from BUPA Study; Br. Med. J.,1994; 308: 363-366. FNT 2. Law M. R., Wald N. J., Thompson S. G.; By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischemic heat disease?; Br. Med. J., 1994; 308: 367-373. FNT 3. La Rosa J. C., Hunninghake D., Bush D., et al.; The cholesterol facts: a summary of the evidence relating dierary fats, serum cholesterol and coronary heart disease: a joint statement by the American Heart Association and the National Heart, Lung and Blood Institute. Circulation 1990; 81: 1721-33. FNT 4. Havel R. J., Rapaport E.; Drug Therapy: Management of Primary Hyperlipidemia. New England Journal of Medicine, 1995; 332: 1491-1498.
Sterols are important cyclized triterpenoids that perform many critical functions in cells. Phytosterols such as campesterol, stigmasterol and beta-sitosterol in plants, ergosterol in fungi and cholesterol in animals are each primary components of the cellular and sub-cellular membranes in their respective cell types. The dietary source of phytosterols in humans comes from vegetables and plant oils. The estimated daily phytosterol content in the conventional western-type diet is approximately 250 milligrams in contrast to a vegetable diet which would provide double that amount.
Although having no nutritional value to humans, phytosterols have recently received a great deal of attention due to their possible anti-cancer properties and their ability to decrease cholesterol levels when fed to a number of mammalian species, including humans. Phytosterols aid in limiting cholesterol absorption.sup.5, enhance biliary cholesterol excretion.sup.6 and shift cholesterol from atherosclerotic plaque.sup.7. While many of the mechanisms of action remain unknown, the relationship between cholesterol and phytosterols is apparent. This is perhaps not surprising given that chemically, phytosterols closely resemble cholesterol in structure. The major phytosterols are beta-sitosterol, campesterol and stigmasterol. Others include stigmastanol (beta-sitostanol), sitostanol, desmosterol, chalinasterol, poriferasterol, clionasterol and brassicasterol. FNT 5. Gould R. G., Jones R. J., LeRoyu G. V., Wissler R. W., Taylor C. B.; Absorbability of B-sitosterol in humans; Metabolism, (August) 1969; 18(8): 652-662. FNT 6. Tabata T., Tanaka M., Lio T.; Hypocholesterolemic activity of phytosterol. II (author's transl.); Yakugaku Zasshi, 1980; 100(5): 546-552. FNT 7. Hepistall R. H., Porter K. A.; The effect of B-sitosterol on cholesterol-induced atheroma in rabbits with high blood pressure; Br. J. Experimental Pathology, 1957; 38: 49-54.
While there is data indicating that one of the major risk factors for atherosclerosis or CVD is the level of blood cholesterol, this risk factor cannot be considered conclusive. It has been found that individuals having serum cholesterol levels within the normal, acceptable range may still be at risk- and do develop atherosclerosis and CVD. For this reason, a more reliable risk factor or indicator is required.
It is an object of the present invention to obviate or mitigate the above disadvantages and limitations regarding CVD risk assessment, treatment and dietary monitoring for those at risk for CVD.